Efficacy and Safety of Coumarin and Troxerutin in the Symptomatic Treatment of Chronic Venous Insufficiency

NCT01848210 | Completed Phase 4 Results

• 3 other identifiers: VN01/12U1111-1141-727715030313.0.1001.5470
• Study Type: interventional
• Target: 829
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of the fixed-dose combination of coumarin and troxerutin versus placebo in the symptomatic treatment of chronic venous insufficiency.

Conditions

Chronic Venous Insufficiency

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Mean Change (Reduction) From Baseline in Volume of Reference Leg at Week 16

  Change in the partial volume of legs will be measured using a water plethysmometer. The volume of water (at 34 ± 0.2 °C) displaced after limb immersion is collected in an empty plastic Beaker which has been previously weighed (scale tare). The equilibrium/stability will be estimated using the absolute difference between measures of volume obtained at the Week 16 visit and Baseline to determine the reduction in edema.

  Baseline and Week 16

Secondary Outcomes (3)

• Change (Reduction) From Baseline in Local Complaint Severity

  Baseline and Week 16

• Overall Assessment by the Investigator

  Baseline and Week 16

• Number of Participants With Adverse Events (AEs)

  Baseline to Week 16

Study Arms (2)

Coumarin 30 mg + Troxerutin 180 mg

EXPERIMENTAL

Coumarin 30 mg, troxerutin 180 mg fixed-dose combination tablets, orally, three times daily for up to 16 weeks.

Drug: Coumarin/troxerutin

Placebo

PLACEBO COMPARATOR

Coumarin + troxerutin placebo-matching tablets, orally, three times daily for up to 16 weeks.

Drug: Placebo

Interventions

Coumarin/troxerutin DRUG

Coumarin + troxerutin fixed-dose combination tablets

Also known as: Venalot®

Coumarin 30 mg + Troxerutin 180 mg

Placebo DRUG

Coumarin + troxerutin placebo-matching tablets

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Consent of subject or legal representative
• Men or women of any ethnicity, aged between 18 and 75 years, and body mass index (BMI) equal or less than 40.
• Is able to use properly the medication according to protocol.
• Has chronic venous insufficiency in the reference leg with the clinical classification C3, or C4a orC4b or C5, provided that in two last situations the present lipodermatosclerosis does not compromise more than 1/3 portion of the leg immersed or immersible in the plethysmometer.
• Has stable edema (in a steady state), equivalent to a variation lower than or equal to 10% in partial volume of the reference leg between the screening visit and the randomization visit, and present for at least 6 months.
• Scoring in "Severity Score of Local Complaints" equal to or higher than 5 total points.
• Women who are using an effective (at the discretion of the investigator), but not hormonal, birth control method (not hormonal intrauterine device (IUD), surgical sterilization, among others), or who are postmenopausal, in addition to condom use (mandatory).

You may not qualify if:

• Has chronic venous insufficiency classified as C1, C2 in the reference leg or C6 in any leg.
• Has chronic venous insufficiency C4b or C5 in the reference leg, with lipodermatosclerosis present in more than 1/3 portion of the leg immersed in the plethysmometer.
• Has unstable edema, equivalent to variation of more than 10% of partial volume in the reference leg between the screening visit and randomization visit, prior to start of treatment.
• Has venous obstruction and/or deep vein thrombosis (DVT) and/or presence of phlebitis in lower limbs during the last 3 (three) months.
• Has developed deep vein insufficiency during the last 3 (three) months.
• Has a history of surgery at the venous system or sclerotherapy or who received any treatment for chronic venous insufficiency during the last 03 months, whether it was by drug, elastic stocking, laser, or surgery.
• Has used previously Venalot® and had no benefits with the treatment.
• Has a previous history of known or suspected allergy or intolerance to any of the ingredients of the medicinal product under investigation.
• Has any clinical finding (history and physical examination) that is interpreted by the physician-investigator as a risk to participant's participation in the study.
• Has known serious systemic disease, according to the medical and/or laboratory history.
• Has history of a known liver disease such as hepatitis A, hepatitis B, or C.
• Has changed at least one lab parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (gamma-GT), or alkaline phosphatase 2.5 times above the upper limit of normal range; hemoglobin less than 10 g/dL; clearance of creatinine estimative equal or above 60mL/min/1.73 m\^2; platelets below 90,000/mL; and total bilirubin and fractions 1.5 times above the normal values.
• Has been using diuretics for a period less than or equal to 6 months due to any disease (hypertension, renal failure, or other).
• Has serious chronic liver or kidney disease, according to the medical and/or laboratory history.
• Has uncontrolled blood hypertension (systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 100 mmHg) at randomization or clinical hypertensive urgency.

Sponsors & Collaborators

• Takeda: lead

Related Publications (1)

• Martinez-Zapata MJ, Vernooij RW, Simancas-Racines D, Uriona Tuma SM, Stein AT, Moreno Carriles RMM, Vargas E, Bonfill Cosp X. Phlebotonics for venous insufficiency. Cochrane Database Syst Rev. 2020 Nov 3;11(11):CD003229. doi: 10.1002/14651858.CD003229.pub4.

  PMID: 33141449 DERIVED

MeSH Terms

Interventions

coumarin; troxerutin; Venalot

Results Point of Contact

• Title: Medical Director, Clinical Science
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2013
• First Posted: May 7, 2013
• Study Start: May 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: November 11, 2016
• Results First Posted: November 11, 2016

Record last verified: 2016-09